Lower Motor Neuron Diseases: An Indepth Review

Lower Motor Neuron Diseases: An Indepth Review

Dr. Pooja Narayanan, Dr. Vidya Krishnan, Dr. M.Shanthi*

SRM Kattankulathur Dental college, SRM University of Science and technology,

Potheri, Kanchipuram- 603203

Abstract:

Motor neuron diseases (MND) are a group of neurological conditions that result in loss of nerve function over a period of

time. They are broadly classified as Upper Motor Neuron Disease (UMND) and Lower Motor Neuron Disease (LMND).

Lower motor neuron disease are those groups of MNDs that arise from the distal motor nerve in the anterior horn cell.

Recent advances in the field of medicine has led to identify the involvement of genetic mutations in the pathophysiology of

the MNDs. It has also aided in nurturing various management techniques. The current review will broadly describe the

different types of Lower Motor Neuron Diseases prevelant and the current evolution in the managing of the patient with

these conditions.

Keywords: UMND- Upper motor neuron disease, LMND- Lower motor neuron disease, SBMA- Spinal and Muscular Atrophy, SMA-

Spinal Muscular Atrophy, dHMN- Distal Hereditary Motor Neuropathy, PMA- Progressive Muscular Atrophy, MMA- Monomelic

Amyotrophy, PPS- Post-Polio Syndrome, GBS- Guillain- Barre Syndrome

INTRODUCTION:

Motor neuron diseases (MND) are gradually developing

disorders of unknown origin which results in degeneration

of motor neurons in cranial nerves nuclei, spinal cord and

pyramidal neurons in the motor cortex [1]. It becomes

clinically apparent during middle ages and is more

common in men [2]. 5-10% of the cases are of familial

origin and of these, 20% is caused by mutation of

Superoxide dismutase (SOD1) gene [1]. The usual

investigations done are: Electromyography (EMG),

Sensory and motor nerve conduction studies, spinal

imaging, brain imaging, CSF examination, etc [1]. The

current review paper discusses elaborately on prevalent

Lower motor neuron diseases and their advancing

managing techniques.

Classification of Motor Neuron Diseases:

Motor neuron diseases are broadly classified into: Upper

Motor Neuron disease (UMND) and Lower Motor Neuron

disease (LMND). In the case of UMND, the patient

becomes hyper-responsive to stretching. They also present

with flexion withdrawal, spasm, etc. The UMN lesion is

more pronounced in the extensors of lower limbs and the

flexors of upper limbs, brisk tensor reflexes, etc. In the

case of LMN lesions, a loss of contraction develops

resulting in weakness and reduced muscle tonicity.

Following this, atrophy of muscles causes muscle wasting

and depolarisation resulting in fibrillation, which can be

detected by electromyogram [1].

LMN- Lower motor Neuron; UMN- Upper Motor Neuron; ALS- Amyotrophic Lateral sclerosis, F-ALS- Familial Amyotrophic Lateral Sclerosis; PLS- Progressive lateral Sclerosis;

PMA- Progressive Muscular Atrophy; SBMA- Spinal and Bulbar muscular Atrophy

Figure 01: Spectrum of Motor Neuron Diseases, according to Statland et.al, 2015 [3]

Pooja Narayanan et al /J. Pharm. Sci. & Res. Vol. 13(1), 2021, 19-29

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GBS- Guillain Barre Syndrome; SBMA- Spinal and Bulbar Muscular Atrophy; dHMN- Distal hereditary motor neuropathy; MMA- Monomelic Amyotrophy; PMA- Progressive muscular

atrophy; LL Predominance- Lower limb; UL - Upper limb; MND- Motor Neuron Disease

Figure 02: Diagnostic Algorithm proposed by Garg et.al, 2016 for LMN [4]

A. Heritable Lower motor neuron diseases:

1. Spinal and Bulbar Muscular atrophy (Kennedy’s

Disease):

Kennedy's disease is also known as Spinal and bulbar

muscular atrophy (SBMA). Kennedy et al, in 1968,

described spinal and bulbar muscular atrophy, in 11

patients taking notice of its X-link recessive pattern.

Harding et.al, in 1982, reclassified it as X-linked bulbo-

spinal neuronopathy. It occurs between the 3rd -5th decades

of life. The disease is found to mainly involve the male

population and minority of the females are carriers and

asymptomatic women are involved in transmission of the

disease. This is because of low level of androgen

circulation and the Androgen Receptor stimulation in

females [5]. In a cross-sectional study by Fratta et.al, 2014

in UK, it was stated that 61 cases of spinal bulbar and

muscular atrophy have been identified in the past decade

[6].

Gene mutation:

It is caused by the mutation of trinucleotide repeat in the

Androgen Receptor (AR) gene. An expanded trinucleotide

repeat of more than 37 glutamine proteins is sought to be

responsible for the disease [5].

Pathophysiology:

The exact pathogenesis of Kennedy’s disease remains

unknown. Intranuclear inclusions consisting of misfolded

polyglutamine-expanded proteins in affected neuronal

populations is evident. The polyglutamine aggregation is

followed by nuclear inclusion and impairment of function.

It occurs as a result of transcriptional dysregulation and

other mechanisms. The endocrine manifestations like

gynaecomastia, reduced fertility, weakness and muscle

atrophy occur due to loss of function mechanisms [5].

Clinical features:

On examination muscle atrophy, decreased, or absent

tendon reflexes, tremor, cramping and fasciculations are

observed [4,5,7].

Figure 03: Clinical features of Kennedy’s disease in

man and mouse [7]. (Men are the ones usually affected

with the condition, and women are merely carriers.)


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Figure 04: The oral manifestation of SBMA [4,5,7]

Sensory manifestation:

Sensory symptoms like numbing and tingling, mainly in

the distal portion of limbs, is observed in later courses of

the disease. In a study by Antonini et.al, in 2000, on the

sensory involvement in Spinal and Bulbar muscular

Atrophy, the assessment indicated the presence of

trigeminal neuronopathy [8].

Others:

Signs of androgen insensitivity, such as testicular atrophy,

gynecomastia, oligospermia, and erectile dysfunction and

decreased sperm count are observed in SBMA affected

males. Carrier females have reported cramping and other

symptoms [7]. Obstructive sleep apnea is common in

SBMA patients. Brugada-like ECG abnormalities are

observed in 4% patients and should be monitored closely

[5].

Investigations:

• Appropriate family history is the first and foremost in

diagnosis of the disease.

• Low sensory neuron actionable potential (SNAP)

amplitude and histopathological studies implies

sensory neuronopathy [7].

• Genetic testing for CAG repeats in Androgen

Receptor is deemed necessary. The normal level of

CAG repeats varies from 11-32 CAGs and the SBMA

population portrays 38-69 [5].

• Laboratory findings like elevated serum creatine

kinase (2-4 times increase) [9], aspartate and alanine

aminotransferase and lactose dehydrogenase(useful

biomarkers evidently showing skeletal muscle

involvement), liver enzymes, total cholesterol , LDL,

triglycerides [7].

• Serum creatinine is considered a useful biomarker in

diagnosing the disease in a study conducted by

Hijikata et.al, 2018 [10].

• Electrophysiologic studies

• PET scans revealed Glucose hypo-metabolism in

frontal lobe areas.

• Histopathological studies

• Swallowing deficits are identified by Video

fluorography with Barium swallow [5,9].

Differential diagnosis:

Differential diagnosis includes ALS, hereditary causes like

SMA type IV, dHMNs (distal hereditary motor

neuropathies). Symptomatic similarities exist between

metabolic myopathies, myasthenia gravis and

polymyositis. Other non-hereditary mimics includes

Progressive Muscular Atrophy (PMA), post-polio

syndromes, Paraneoplastic syndrome (PNS), toxins like

lead poisoning, etc [5].

Prognosis:

It has been observed that these patients show good

mobility preservation until the late stages of disease.

Patients can initially reveal dysarthria, which may

progress to dysphagia. Although the life expectancy is not

significantly reduced, risk of choking and aspiration

pneumonia are higher in selected patients due to bulbar

dysfunctions[5].

Management and current trends:

The target of clinical trials conducted is to reduce the

Androgen Receptor ligand repeats in SBMA patients, but

this has not been the case of the therapeutic strategies

experimented till date.

Table 01: The given table summarises completed

studies according to Author, Year and the study

performed and their outcomes [5].

Author,

Year Study done Outcome

Katsuno

et.al, 2003

Leuprorelin rescues

polyglutamine-

dependent

phenotypes in a

transgenic mouse

model of spinal and

bulbar muscular

atrophy.

In transgenic mouse

models- Positive

outcome

Fernandes

et.al, 2011

Efficacy and safety

of Dutasteride in

patients with spinal

and bulbar muscular

atrophy: a

randomised placebo-

controlled trial.

No effect

Querin

et.al, 2013

Pilot trial of

Clenbuterol

in spinal and bulbar

muscular atrophy

Increase in the 6-min

walk test and

forced vital capacity

after 12 months.

Hashizume

et.al, 2017

Long-term treatment

with Leuprorelin for

spinal and bulbar

muscular atrophy:

Natural history-

controlled study.

Recent study

conducted in man-

delay the functional

decline and suppress

the incidence of

pneumonia and death

in SBMA patients


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2. Spinal Muscular Atrophy:

The term “spinal muscular atrophy (SMA)” refers to a

group of genetic disorders characterized by degeneration

of anterior horn cells and resultant muscle atrophy and

weakness. Currently, data reveals the incidence rate of this

disease to be 1:11,000. Male population is more affected

[11].

Genetic involvement:

It was first revealed in 1995, in Melki Laboratory that 95%

of SMA cases reported, are caused by homozygous

deletion of SMN (Survival Motor Neuron) 1 gene on

chromosome 5q13 [12]. In humans, two forms of SMN

gene exists: a telemeric form (SMN 1) and centromeric

form (SMN 2). Patients lacking a functioning SMN 1

gene, are dependent on SMN 2 gene, to produce the SMN

protein. Due to exclusion of exon 7 in 85% of the cases,

the SMN protein renders non-functional. This leads to

deficiency of the SMN protein and in turn causes SMA

[13].

Pathophysiology:

SMN functions as a multiprotein complex and is found

throughout the cytoplasm and nuclei, which is important in

splicing and ribonuclear biogenesis. Another school of

thought is the downstream consequences of altered RNA

processing that results in non-favourable motor neuron

survival or development or both [13].

Clinical features:

Figure 05:The given chart summarises the general

clinical features observed in SMA patients [13,14]

SMA doesn’t have any major oral manifestations. It was

presented with multiple phenotypes which were

categorised into 4 types in 1991 by the Muscular

Dystrophy Association. The classification was based on

motor function and age of onset. (Table 02).

TABLE 02: The table summarises the classification of SMA on the basis of motor function and age of onset [1].

TYPE ONSET INHERITANCE FEATURE PROGNOSIS

TYPE 1

Werdnig- Hoffman Infancy Autosomal recessive

Severe muscle wasting/

weakness, Chances of

respiratory failure

Poor

TYPE 2

Kugelberg-

Welander

Childhood,

adolescence Autosomal recessive

Proximal weakness and

wasting, EMG shows

denervation

Slowly progressive

disability

TYPE 3

Distal forms Early adult life

Autosomal

dominant

Distal weakness and wasting

of hands and feet

Good, Seldom

exhibits disability

TYPE 4

Bulbospinal

Adult life, males

only X-linked

Facial and bulbar weakness,

proximal limb weakness,

gynaecomastia

Good

Investigation:

Table 03 : The table summarises the different

diagnostic criteria for determining the presence of

Spinal Muscular Atrophy [12]

• Familial history

• Presence of proximal muscle weakness,

• Reduced/ absent deep tendon reflexes

• Identify variants of SMN1 on molecular genetic testing

Differential Diagnosis[15]:

Congenital- Myotonic Dystrophy Type 1, Congenital

Muscular Dystrophy, Congenital Myasthenic

Syndrome,etc

Later Childhood- Guillain Barre Syndrome,

Hexosaminidase A deficiency, Monomelic

Amyotrophy,etc

Adulthood- Spinal and Bulbar Muscular Atrophy,

Amyotrophic Lateral Sclerosis

Prognosis-

The new developments in management of this neuronal

condition, will presumably improve the natural history of

the condition. Newborn screening programs, targeted

therapy and diagnosis prior to development of symptoms,

will decrease the morbidity and mortality [15].


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Management:

The past decade has shown marked improvement in the

clinician's ability to manage patients of this neuronal

condition.

Table 04: The table summarises the different organ

systems that need evaluations and the possible

assessments, evaluation and aids that can be done [15].

Organ System Aids

Gastrointestinal/

Feeding

• Evaluate for Feeding

dysfunction, Gastroesophageal

reflux,Constipation;

• Consider gastric tube placement

in cases with dysphagia or

aspiration risk

Respiratory • Evaluate for Forced Vital

Capacity (FVC), Assess pulse

oximetry and capnography,

airway clearance, Consider

Polysomnogram

• Refer to a pulmonologist

• SMA I and II are generally

weak, and are of concern for

nocturnal hypoventilation

Musculoskeletal • Orthopaedic therapy,

physiotherapy, Occupational

Therapy evaluation and

rehabilitation is important

• Assess the gross and fine motor

skills

• Contractures and hip dislocation

Scoliosis

• Need for ambulatory aids

Miscellaneous • Genetic counselling

• Family support and resources

• Use of community or online

resources Need for social work

involvement Home nursing

needs

CURRENT ADVANCEMENTS IN SMA

TREATMENT:

• Lunn, in 2008, tabulated various clinical trials that

were ongoing or completed in molecular genetics. He

concluded that the implications of these trials will

improve the standard of care for patients and cure this

devastating neurodegenerative disease [14].

• Many different methods like small molecule therapy,

RNA- based therapy and gene therapy have evolved.

• In 2016, The Food and Drug Administration approved

the use of NUSINERSEN (SPINRAZA) . The

recommended dosage is administered intrathecally in

doses of 12 mg (5 mL). The treatment is initiated by 4

loading doses of the drug. The first 3 doses are given

in a 14 days interval and the last one is administered

30 days after the 3rd dose. Every 4 months after the

4th dose, a maintenance dose is provided [16].

• In a study by Mendell and his colleagues reported in

2017, 15 patients with SMA 1 were provided with a

single dose of IV adeno-associated virus serotype 9

carrying SMN complementary DNA encoding the

SMN protein. 3 patients received low dose, and 12

received high dose. All patients were alive and event

free for a period of 20 months. Of those patients who

received high doses, 11 were able to sit unassisted, 9

were able to roll over and could speak and 2 of them

were able to walk independently. The use of

prednisolone was observed to increase the serum

aminotransferase levels in 4 patients. It resulted in a

longer survival rate, making the patient achieve motor

milestones and accentuate their inherent motor

functions. But, due to smaller study group, further

studies are required to confirm the findings of this

single gene therapy [17].

3. Distal Hereditary Motor Neuropathy (dHMN)

Distal Hereditary Motor Neuropathies (dHMN) are a

group of genetically occuring heterogeneous diseases due

to LMN weakness. The condition is thought to begin

during the first two decades but onset in the third decade is

also common [18].

Classification:

Table 05: The given table describes the different types

of Distal Hereditary Motor Neuropathy, traits, features

and Gene mutation as elucidated by Harding et.al, in

1993 [19].

TYPES TRAIT FEATURES GENE

MUTATION

Type 1 Autosomal

Dominant

Juvenile onset,

distal wasting

and weakness

HSPB1

HSPB8

Type 2 Autosomal

Dominant

Adult onset with

distal wasting

and weakness

HSPB1

HSPB8

BSCL2

Type 3 Autosomal

Recessive

Slow

progressive

wasting and

weakness

unknown

Type 4 Autosomal

Recessive

Slow

progressive

wasting and

weakness with

diaphragmatic

paralysis

unknown

Type 5 Autosomal

Dominant

Upper limb

predominance

GARS

BSCL2

Type 6 Autosomal

Recessive

Spinal muscular

atrophy with

respiratory

distress type 1

IGHMBP2

Type 7 Autosomal

dominant

Adult onset with

vocal cord

paralysis

DCTN1

TRPV4

X-linked

dHMN X-linked

Distal-onset

wasting and

weakness

ATP7A

dHMN and

pyramidal

features

Autosomal

dominant

DHMN with

pyramidal

features

SETX

BSCL2


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Figure 06: The given figure elucidates the cardinal

features of Distal Hereditary Motor Neuropathy [18]

Upper limb predominance, Vocal Cord paralysis,

respiratory distress and pyramidal features are seen in

some patients [4]. Oral manifestations are not majorly

manifested.

Investigation:

• In EMG chronic distal predominant denervation is

observed [18].

• Neurophysiologic studies enables to differentiate

between Charcot Marie and dHMN [18].

• In a genetic study by Tsai et.al, in 2017, on Taiwanese

population, it was demonstrated that dHMN can be

caused by mutation of WARS gene (responsible for

tryptophan production and angiostasis), and identifies

the probable pathogenic role of t-RNA synthetases in

inherited neuropathies [20].

• Next-generation sequencing [4]

Differential diagnosis-

Myoshi Myopathy, Charcot Marie Tooth disease,etc [18].

B. Acquired Lower motor Neuron diseases:

1. Progressive muscular Atrophy (PMA)

Progressive Muscular Atrophy (PMA) is a rare, sporadic,

adult-onset, clinically isolated LMN syndrome due to the

degeneration of LMNs, including anterior horn cells and

brainstem motor nuclei [21]. In 1850, a French

neurologist, Aran, and Duchenne coined the term PMA.

Therefore, PMA is sometimes referred to as Aran-

Duchenne or Duchenne-Aran disease [22]. Cruveilhier in

1853, autopsied Aran‘s patients and revealed atrophy of

the ventral spinal roots and the motor nerves providing the

first evidence of PMA being a neurogenic disorder. It

accounts for 5% of adult-onset MNDs. Men are more

commonly affected and are found in the older age group

(mean age: 63.4+/- 11.7 years) [23].

Evidence reveals subclinical UMN involvement in

radiographic or neurophysiologic examination despite its

clinical absence [21,24]. The life expectancy when

compared with ALS patients is longer. At present,

sporadic patients with MND having purely LMN

symptoms on examination are termed PMA, who could

possibly develop UMN features in future [21].

Pathophysiology:

It is caused by LMN and spinal cord degeneration. In a

study by Geser, 2011, 43 kDa transactive responsive

sequences DNA binding protein (TDP- 43) is the most

commonly found inclusion body in motor neuron disease

[25]. Although many genetic mutations were identified in

anterior horn cell degeneration eg: SOD1, SMN1, etc;

majority were absent in PMA [26]. At present, the exact

pathogenesis is unknown [21].

Clinical features:

Figure 07: The given figure summarises the clinical

features of PMA [21].

INVESTIGATION:

Table 06: Table given table describes the various

investigations done for treating the condition briefly

[26].

Electrophysiologic- It confirms active and chronic

denervation

Nerve conduction studies- low to normal compound

motor amplitude potential

Needle EMG- Various spinal segments reveals active

denervation in forms of fasciculations, fibrillations, and

unstable MUPs

Diffusion Tensor imaging- reduced fractional anisotropy

along corticospinal tracts; transcranial magnetic

stimulation which shows prolonged central motor

conduction

Imaging biomarkers [21]:

• Imaging biomarkers of UMN involvement include

diffuse tensor MRI (magnetic resonance imaging)

and MRS (magnetic resonance spectroscopy).

• Neurophysiological biomarkers of UMN involvement

are TMS (transcranial magnetic stimulation) and

Beta-band intermuscular coherence (relatively new

technique, evidentially reliable marker).


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Prognosis:

Rate of progression can vary. In a comparison study by

Kim et.al, in 2009, the mean survival duration in patients

with PMA and ALS were estimated in 200 months. It was

found that PMA patients had a 12 month longer survival

period when compared with ALS patients. A shorter

survival rate has been associated with several factors like:

(1) axial onset, (2) ALSFRS-R at diagnosis less than 38,

(3) involvement of more segmental regions, (4) baseline

forced vital capacity (FVC) less than 80% of the predicted

value, (5) a sharp decline in FVC within the first 6 months.

Patients presenting with a history of 4 years of PMA with

weakness restricted to distal or proximal muscles have a

favourable prognosis [27].

Differential diagnosis [26]:

Immune neuropathies- Multifocal motor neuropathy;

Paraneoplastic neuropathies;

Degenerative conditions- SMA, bulbospinal atrophy,

Hirayama disease,

Amyotrophy as a dominating feature in- Tay-Sachs

disease, porphyria, etc.

Management:

There is no specific management for treating patients of

this neuronal population. It is recommended to follow the

therapeutic strategies used in case of patients with ALS

[26]. Regular surveillance and symptomatic management

is considered mandatory.

Table 07- Summarises the therapies required and their

intervention for ALS, as mentioned by Statland, in

2015 [3]

Therapy Intervention

Respiratory

Non-invasive positive pressure

ventilation, cough assist, oral

suctioning

Speech Therapy Percutaneous gastrostomy tube for

nutrition

Hypersalivation Include anticholinergic medication,

botulinum toxin, xerostomic agents

Physical and

Occupational

therapy

Ambulatory services, braces, etc.

Psychological Counselling for patients and family

2. Monomelic Amyotrophy (Hirayama Disease)

In the 1950s, Hirayama first described monomelic

amyotrophy. It was later referred to as Hirayama disease

(HD). It has been mainly reported to occur in Japan, China

and India. It affects males mostly (Male : Female= 7:1)

and in the younger age group (adolescents to 3rd decade of

life) [28,29].

Clinical features:

Figure 08: The given figure depicts the clinical features

of Monomelic Amyotrophy [29]

Pathogenesis:

Although the pathophysiology is uncertain, it may involve

damage of anterior horn cells. Displacement of the

posterior cervical dural sac on neck flexion resulted in

cord compression and/or venous congestion. It's non-

progressive, purely motor focal amyotrophy in distribution

of C7, C8, T1 spinal innervated muscles [29].

Genetic studies:

In a clinical study by Misra et.al, in 2005, on the SMN

motor gene deletion in relation to Hirayama disease, it was

concluded that SMN gene deletion was not found.[30]

In a mutational analysis of Glycyl- tRNA synthetase

(GARS) gene in Hirayama disease, by Blumen et.al, in

2010, no pathogenic mutations were found, excluding its

possibility as an etiologic factor in Hirayama Disease

(HD).[31]

Investigation:

• CSF analysis, muscle enzyme levels.

• Motor nerve conduction studies reveal reduction in

the ulnar compound muscle action potential (CMAP)

when compared with median CMAP.

• Sensory nerve conduction studies.

• In 2006, studies on somatosensory potential by Misra

et.al, revealed amplitude reduction in cervical

response during neck flexion, which indicates

overstretching of cervical cords due to subclinical

damage to sensory fibers [32].

• MRI scans portrayed flattening of spinal cord against

C5 and C6 vertebral bodies


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• Electromagnetic induction helps examine motor

functions [29].

Management:

• If the condition is recognized early, the use of cervical

collars for a timer period of 3-4 years is considered to

relieve the patient of progressive muscle weakness

and thus reducing the impact of the condition [33].

• In a systematic review by Bembenek, in 2020, the use

of Noninvasive brain stimulation with Transcranial

Magnetic Stimulation (TMS) has been reviewed. All

studies in HD patients focused on single-pulse motor

evoked potentials (MEPs). The systematic review

remains inconclusive due to lack of evidence. Hence,

further studies are indispensable to confirm the

usefulness of this method [34].

C. Acute Lower Motor Neuron Diseases:

1. Post- polio Syndrome (PPS)

PPS is an acute type of LMN that occurs many years

following episodes of poliomyelitis [35]. It usually occurs

after 30 to 40 years after initial polio virus attack. It is

more commonly seen in females. It is characterised by

progressive weakness and atrophy of joints and muscle

pain[36]. 15-80% of paralytic polio survivors develop

post-polio syndrome. A recent study, by Bertolasi et.al, in

2016, on a 50 year follow up of Polio patients in North

Italy, revealed the prevalence of the disease to be 42%

[37].

Pathophysiology:

There is a marked increase in motor unit areas caused by

collateral sprouting of adjacent motor neurons in the spinal

cord. The motor unit area is said to increase upto 20 times,

reaching a level where no further reinnervation is possible.

Due to uncompensated denervation, loss of muscle

strength and atrophy of muscle fibers occurs. The

underlying cause of denervation is still unclear. The

different hypotheses that have been proposed are [38]:

• stress or overuse of motor units

• Ageing

• Persistent virus

• Immunological factors and chronic inflammation

• Genetics

Gene involvement:

• Bartholdi et. al, in 2000, in his brief report on the gene

involvement in PPS, identified the absence of SMN

gene deletion [39].

• In 2002, Rekand et. al, and his colleagues, identified

polymorphism in Fc- gamma receptor III A as a

causative factor of post-polio syndrome [40].

• In 2014, in a study by Saurabh Kumar et.al and his

colleagues, out of 110 patients, only 50 patients

(45.46%) showed polymorphism in exon 2 of PVR

gene. They concluded that the disease progression is

associated with PVR gene [41].

Diagnostic criteria:

The diagnostic criteria for Post-poliomyelitis are, period of

recovery following acute poliomyelitis, gradual onset of

muscle weakness, joint pain, sleeping problems and prior

paralytic poliomyelitis.

Investigation:

Table 08: The given table summarises the various

clinical signs and investigations [38].

Clinical signs Investigation

Muscle

function

Weak or no muscle

strength, flaccid

paralysis

Clinical

examination

Electromyography

MRI

Tendon

reflexes

Weak or no tendon

reflexes

Clinical

examination

Sensory

function

No sensory loss, cold

intolerance might be

present

Clinical

examination Nerve

conduction

velocity

Cranial

nerves

Most often normal

but might be

impaired (bulbar

poliomyelitis)

Clinical

examination

Investigation on

oesophageal and

laryngeal muscle

function

Pulmonary

function

and sleep-

disordered

breathing

Weak respiratory

muscles, chest wall

and spinal

deformities Daytime

sleepiness

Pulmonary

investigation,

including complete

spirometry

Polysomnography

Differential diagnosis:

Conditions like Amyotrophic Lateral sclerosis, tumors of

the cervical and thoracic cord cervical spondylosis, other

causes of chronic fatigue syndrome, myasthenia gravis,

myopathies and chronic systemic infections are are the

differential diagnosis for PPS [36].

Management:

There is no cure of PPS. Symptomatic treatment that

improves the quality of life is the main goal in

management of the condition. Symptomatic management

can be dealt with analgesics and antidepressants.

Physiotherapy, physical activity and muscle training:

The European Neuromuscular Centre Workshop in 1994,

recommended guidelines for exercise that are still valid.

TABLE 09: The given table describes the condition of

the patient and the physical training that can be done

for the patient [38].

Condition of the patient Physical Training

Near- normal strength, no

signs of reinnervation Heavy resistance training

Moderate Paresis with signs

of reinnervation

Submaximum Endurance

Training

Severe Paresis Avoid muscle training.


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Pharmacological treatments:

TABLE 10: The given table discusses about the different

clinical trials done in the field of Pharmacology in

management of Post-Polio Syndrome [38].

Author,

Year Clinical Trials Outcome

Horemans

et.al, 2003

Pyridostigmine in

postpolio syndrome:

no decline in fatigue

and limited functional

improvement.

A marked

improvement in

walking

Gonzalez

et.al, 2004

Prior poliomyelitis-

IVIg treatment

reduces

proinflammatory

cytokine production.

Marked decrease

in the quantity of

proinflammatory

cytokines

Vasconcelos

et.al, 2007

Modafinil for

treatment of fatigue

in post-polio

syndrome: a

randomized

controlled trial.

Ineffective

Skough

et.al, 2008

Effects of resistance

training in

combination with

coenzyme Q10

supplementation in

patients with post-

polio: a pilot study.

No significant

result

Surgery:

Limb length inequality, joint deformities and arthrosis

require surgery. Secondary disorders like spinal stenosis,

disc hernia require surgical intervention.Due to increased

sensitivity of patients of this neuronal population to

anesthetics, the patient should be monitored carefully

throughout the procedure [38].

• Guillain Barre Syndrome (GBS)

It was initially described in 1916 [42]. GBS is

characterised by rapidly progressive weakness of arms and

legs and in some patients involves the bulbar and

respiratory muscles too [43]. GBS incidences vary

between 0.4 and 3.25 cases per 100,000 per year. It occurs

due to precipitated infection. Infectious agents like

cytomegalovirus, herpes simplex virus, Epstein Barr virus,

Influenza, etc, have been found to be associated with the

disease. Recent surgeries have also found to be associated

with the condition [44].

Pathogenesis:

It is a post-infectious immune-mediated nerve injury of 3

phenotypes: (1) Purely demyelinating (2) Purely axonal

(3) demyelinating with axonal involvement. It is an

antibody mediated reaction. Antibodies binding to GM1 or

GD1a gangliosides activate myelin destroying

complements [42].

Clinical features:

Table 11: The given table describes the different

clinical features of Guillain Barre Syndrome [42.44]

Severe back pain, distal limb parasthesia- “ tight band”

feeling

Areflexia and weakness

Weakness- Rapid, ascending pattern Weakness of

oropharyngeal and facial muscles

Dysesthesia of feet and hands

Symmetric limb weakness, decrease or loss of reflexes and

objective sensory findings

Ophthalmoparesis- a rare finding (Associated with Miller-

Fisher Syndrome)

Investigation-

Figure 09: The figure elucidates carious Investigations

required for Guillain Barre Syndrome [42]

Management:

Table 12: The given table describes management of

Guillain Barre syndrome patients [42]

Due to loss of ambulation, expert nursing is

mandatoryDue to loss of ambulation, expert nursing is

mandatory

Tests checking swallowing dysfunction, aspiration risk are

necessary

Enteral nutrition is necessary in many patients

Pneumatic compression devices- to avoid deep vein

thrombosis in paralysed leg

Physical therapy in early stages

Cramping- relieved by narcotics; Other drugs like

Carbamazepine or gabapentin are also given

Plasma therapy

IVIg


27

CONCLUSION:

Lower motor neuron diseases include a broad spectrum of

conditions with numerous pathologic and genetic causes.

It is important to combine clinical assessment with

neurophysiologic findings so as to establish accurate

diagnosis. The recent advancements in genetic studies and

imaging techniques have increased the quality of life for

the patient and has magnified the treatment options

available. Although the studies conducted provide a

positive outcome, some of them lack prospective evidence.

Nevertheless, the genetic analysis and developing imaging

techniques are bound to bring forth a better insight into

understanding the pathophysiology of various lower motor

neuron diseases prevalent. This is turn will enable the

medical and paramedical practioners to gain a better

insight in managing patients with these conditions.

Ethical approval:Not applicable

Acknowledgement:None.

Conflict of Interest:The authors have no conflict of

interest.

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Lower Motor Neuron Diseases: An Indepth Review

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